Nephrology - Nephrotic Syndrome

7/27/2019 Nephrology - Nephrotic Syndrome

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Proteinuriaand the

Nephrotic Syndrome


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Clinical vignette

The patient denies use of any medications. Inrecent months, he has had slightly decreasedenergy level and continues to work full time as along-distance truck driver.

P/E: wt 100 kg, BP 140/80; 3+ bilateral pittingedema to the knees. The remaining exam isnormal.

Urinalysis: 3+ proteinuria and 1+ hematuria by dipstick


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Chemical Analysis

Urine Dipstick

Glucose

Bilirubin

Ketones

Specific Gravity

Blood

pH

Protein

Urobilinogen

Nitrite

Leukocyte Esterase


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Negative

Trace

+ (30 mg/dL)

++ (100 mg/dL)

+++ (300 mg/dL)

++++ (2000 mg/dL)

The Urine Dipstick:Protein

Chemical Principle

H

H

H

H

H

H

Pr

Pr

Pr

Pr

Pr

Pr

Protein Error of Indicators Method

Pr

Pr

Pr

Pr

Pr

Pr

Tetrabromphenol Blue

(buffered to pH 3.0)H+

H+

H+H+

H+

H+

Read at 60 seconds

RR: Negative


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Microscopy: 0-4 RBC/hpf, numerous hyaline casts.Some lipid inclusions, revealed by Maltese cross

formation under polarized light.

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http://www.medicine.uiowa.edu/cme/clia/images/testID

20/UA054.jpg


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Microscopic Examination

Oval Fat Body


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Nephrotic Syndrome:features

Proteinuria > 3.5 g/day

Edema Hypoalbuminemia

Hyperlipidemia

Lipiduria HTN


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Nephrotic Syndrome

Nephrotic range proteinuria adults >3.0-3.5 grams/d

Clinical features

Proteinuria Edema Hyperlipidemia Hypoalbuminemia

Hypercoagulable Urinary loss of anti-thrombin III and plasminogen Hemoconcentration

Risk of Infections


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Nephrotic Syndrome:a histologic classification

Minimal Change Disease

Membranous Glomerulopathy

Focal Segmental Glomerulosclerosis

Membranoproliferative GN


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Nephrotic Syndrome

Primary Secondary

Minimal Change Disease NSAIDS

Lymphoma

Focal SegmentalGlomerulosclerosis

Diabetic glomerulosclerosisHIV

Heroin

Obesity

MembranousGlomerulopathy Solid tumorsSLE (lupus nephritis)

Hepatitis B

MembranoproliferativeGN

Hepatitis C

Primary = de novo renal disease = idiopathic


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Nephrotic syndrome associatedwith systemic disease

Amyloidosis

Paraproteinemias


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Evaluation

History and Physical Exam

Urinalysis

Lab Studies

Renal Biopsy


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Differentiate based onurine sediment findings

Nephrotic Nephritic Chronic GN

proteinuria > 3.5 g < 1 g variable

rbcs minor, if any significant variable

casts fatty casts,lipid droplets

rbc casts broad waxy casts


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Examples of casts

rbcs and rbc casts

broad waxy cast


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Examples of casts

Fatty casts


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Diagnostic Approach

Urine protein:creatinine ratio

Serum electrolytes, BUN, creatinine, lipid profile, serumalbumin

Serological work up - depends upon the clinicalpresentation - common serological tests done areSLE:Hepatitis:Diabetes mellitus:Amyloidosis

Nephritic/nephrotic

Renal Ultrasound

Renal Biopsy - Indications

ANA; Anti-ds DNA

Hepatitis B and C serologiesHgb A1c

SPEP; UPEP

C3, C4


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Serum creatinine 1.2 mg/dl Serum Albumin 2.1 g/dl

Serum Cholesterol 350 mg/dl

Serum Triglyceride 800 mg/dl

24 urine collectionCr 2.4 GProtein 11.0 G

Renal USG both kidneys approx 13 cm in length

Renal Biopsy

Our Patients Data


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Minimal Change Disease:clinical clues and features

o Most common in children

o Patient usually normotensive, nephrotic sediment,

normal renal function.

Secondary Etiologies:Idiopathic

Drugs

NSAIDToxins Mercury, LeadInfections HIV, MononucleosisTumors Hodgkin disease


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Focal Segmental Glomerulosclerosis:clinical clues and features

o Most common primary renal disease in African-Americans

o Patient usually hypertensive. Usually progressesto ESRD over 5-20 years

Secondary Etiologies:

IdiopathicDrugs Intravenous heroinInfections HIVOthers reflux nephropathy, obesity


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Focal involving some but not all the glomeruliSegmental involving a part of glomerulus


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Diabetic Nephropathy

Most common cause of nephrotic syndrome in adults Leading cause of ESRD in USA

30% of patients with Type I and 20% of patients withType II DM develop diabetic nephropathy. Initially microalbuminuria followed by heavy

proteinuria and decline in renal function.

Diagnosis usually made on clinical grounds and biopsynot needed ( unless no retinopathy present) Upto 30 % without retinopathy might have

another etiology for there nephrotic syndrome


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Diabetic nephropathy timeline

Harrisons textbook of internal medicine


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NEJM 1999


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Pathology

KimmelsteilWilson

Lesion

Kimmelstein-Wilson lesion

What is this called?


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Interventions for DiabeticNephropathy

Control hypertension

Control proteinuria with use of ACE inhibitorsand/or ARB

Optimize blood glucose control

Control hyperlipidemia

Smoking cessation


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Membranous Nephropathy:clinical clues and features

o Most common cause of idiopathic nephroticsyndrome in Caucasian adults.

o Heavy proteinuria is common. Hypertension andazotemia develops as disease progresses

o Increased incidence of renal vein thrombosis.

Secondary Etiologies:Drugs NSAIDs, Gold, PenicillamineInfections Hepatitis B, syphilisTumors CarcinomaImmunologic SLE, RA


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Membranous GN:histopathology

Key pointsSilver stain GBM thickening,

spikes and traintracks.

Subepithelial Deposits

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lpath/t16.jpg&imgrefurl=http://www.gamewood.net/rnet/renalpath/ch3.htm&h

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%3D20%26ndsp%3D20%26um%3D1%26hl%3Den%26sa%3DN


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Prognosis ofMembranous Nephropathy

Rule of 1/3 1/3 Spontaneous remission 1/3 Partial remission / slow deterioration 1/3 Progress to ESRD


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Membranoproliferative GN:clinical clues and features

Accounts for about 5% of patients with nephroticsyndrome

Associated with a myriad of underlying disorders,including most commonly hepatitis C.

This diagnosis warrants a thorough evaluation tosearch for associated lymphoma, SLE and infection

Accompanying hematuria and the only one of thenephrotic syndromes associated with low serumcomplement level.

MPGN


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MPGN:HistopathologyNormal glomerulus


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Amyloidosis

Amyloid is a proteinaceous material whichaccumulates between cells and produces atrophy anddeath of these cells.

Biochemical forms

Amyloid AL Immunoglobulin originAmyloid AA Inflammatory statesOther


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Amyloidosis:Histopathology

Key features:

Amyloid is hyaline, eosinophilic

Congo Red +

When polarized: green birefringence

EM: Small non-branching fibrils


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How to Remember All this?

Look for clues in history and lab results

Place the case in a broad category like nephroticsyndrome, nephritic syndrome etc

Look for key features in the pathology slides Just remember key features.

Summary principles


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Condition Key Features

Minimal change Normal looking glomeruli

Foot process fusion onEM

FSGS

Diabetes

Segmental sclerosis

Nodular sclerosis

KW lesions

Membranous Silver stain thick BM

spikes, tram-trackAmyloidosis Congo red positive, green

birefringence, fibrils -EM

General treatment principles for


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Control of blood pressure Control of proteinuria with use of

ACE/ARB inhibitors Avoidance of nephrotoxic agents

(eg NSAIDs) Treat underlying condition Control of hyperlipidemia Smoking cessation

General treatment principles fornephrotic syndromes

(non-proliferative GNs)


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What is your differentialdiagnosis of this problem?

Allergic reactions

Angioedema Nephrotic syndrome

Hypothyroidism

Cellulitis

Dermatomyositis

Periorbital edema


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Queries

You next check a urinalysis, which reveals thefollowing:

Does this change yourdifferential diagnosis?

Glucose -

Bilirubin -

Ketones -Specific Gravity 1.015

Blood -

pH 6

Protein 3+

Urobilinogen -

Nitrite -

Leukocyte Esterase -


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Queries

You examine the urine sediment and see the following:

What are these findings and how would you proceedin the workup of this patient?


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Queries

If you suspected a patient had a diagnosis of diabeticnephropathy, would the presence of retinopathy make

this diagnosis more or less likely?

What are some potential complications of nephrotic

syndrome?

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Nephrology - Nephrotic Syndrome